S159: QUÉBEC CML RESEARCH GROUP ANALYSIS OF TREATMENT PATTERNS IN CHRONIC MYELOGENOUS LEUKEMIA: SWITCHING IS DRIVEN BY INTOLERANCE AND SIMILAR ACROSS TYROSINE KINASE INHIBITORS AND LINES OF TREATMENT
Authors: L. Busque, M. Harnois, N. Szuber, R. Delage, L. Mollica, H. Olney, P. Laneuville, S. Sirhan, G. Cournoyer, I. Chamakhi, M. Lalancette, D. Talbot, V. Éthier, P. Desjardins, S. Assouline
Journal: HemaSphere (2022)

Background: In 2001, imatinib was the first tyrosine kinase inhibitor (TKI) approved for the treatment of chronic myelogenous leukemia (CML) which translated into a revolution in the management of this disease. The arsenal of TKIs was progressively reinforced with the addition of other TKIs such as dasatinib, nilotinib, bosutinib, ponatinib and recently asciminib. Two decades of clinical trials have provided critical insight into differential efficacies and specific toxicity profiles of these TKIs supporting the development of guidelines such as the European Leukemia Net (ELN) and the national comprehensive cancer network (NCCN). Real-world evidence studies provide unique and complementary information on treatment patterns, efficacy, side effects and may help identify unmet medical needs of CML patients Aims: This study was aimed at studying frequency of TKI switching, reason for switch, duration of treatment without switching as a function of line of treatment and specific TKI using the real-world data of the Québec registry created in 2009 Methods: Patients with Philadelphia positive (Ph+) CML were recruited with informed consent in the Québec registry. 795 patients were included in this analysis. Data from the registry were extracted July 31ist 2021. Switching was defined as a change of a specific TKI to another. Reasons to initiate switching were categorized as resistance (primary and secondary) or intolerance (hematological or non-hematological). Standard statistical methods were used to evaluated bivariate and continuous variables. Kaplan-Meier curve were used to evaluate overall survival and survival without switching (JMP® Pro 14.1 software, SAS Institute, Cary, NC, USA). Results: At the time of data collection, the median time of follow-up was 7.5 years. Proportion of switching per line of treatment: 1st: 357/795 (44.9%); 2nd: 157/357 (43,9%); 3rd: 59/157 (37,6%); 4th:23/59 (39%). The reason for switching (ratio intolerance/resistance) for each line were: 1st: 1.33; 2nd: 4.3; 3rd: 2.4; 4th: 2.7. 20 patients switched serially across all lines for intolerance and only 3 for serial resistance. Survival without switching was evaluated using a Kaplan-Meier curve by line of treatment and by specific TKI (Figure 1). The survival without switching was similar for patients on imatinib, dasatinib or nilotinib in first line as in second line. In third line, there was no difference between imatinib, nilotinib, dasatinib or bosutinib although numbers of patients were small. We then compared the survival from diagnosis of patients that remained in first or second line versus the patients that reached third or more lines of treatment. Although the mean age at diagnosis and SD were identical between the two groups (54,8 years and SD 15,2) there was a statistically significant difference in survival in favor of patients needing only 1 or 2 lines of treatment (P= 0.0254). Image:Summary/Conclusion: We demonstrate: (i) that switching of TKI is frequent and mainly driven by intolerance in all lines of treatment; (ii) serial intolerance is 6.6 time more frequent than serial resistance suggesting a class effect for intolerance in some patients; (iii) all TKIs have a similar «retention level» in all lines of treatment; (iv) that patients necessitating 3 or more lines of treatment have a survival disadvantage. Our results suggest that one of the most important unmet medical need in CML management is availability of better tolerated drugs